Integration of resources and studies to elucidate neuropeptide signaling Abstract Elucidating the mechanisms governing drug addiction requires knowledge of the role of neuropeptides on the neuronal networks. These signaling peptides mediate responses to environmental stimuli and influence addiction behaviors. Many drugs of abuse directly interact with neuropeptide receptors, and others appear to mediate peptide responses. NIDA has a long tradition of supporting fundamental neuroscience research that has lead to the elucidation of signaling systems and provided critical insights into substance abuse and behavior. Signaling peptides have been studied using a wide range of techniques and model organisms. Multiple complementary neuropeptide repositories and peptidomic and transcriptomic experiments are now available. Even with such information, the challenge remains to gain a complete and systematic understanding of the neuropeptidome and its association with drug escalation and abuse. We propose to address this challenge by developing a public and comprehensive neuropeptide resource much needed by the research community and by collectively analyzing proteomic and transcriptomic experiments to augment the understanding of extracellular signaling peptides both at the fundamental neuroscience as well as the applied substance abuse levels. To accomplish these objectives, we plan to (Aim 1) integrate complementary peptide repositories and develop tools to assemble and effectively query a comprehensive and public resource of experimental and in silico predictions;mine this resource to (Aim 2) perform secondary and joint analysis of available high proteomic experiments;and (Aim 3) perform integrated analysis of proteomic and transcriptomic experiments. The overarching strategy is to integrate complementary information across databases, experiments and platforms to provide a unique and comprehensive understanding of the dynamic neuropeptide complement. The outcome of this project will be resources, tools and information that will fill critical gaps in the knowledge on intercellular signaling systems and suggest targets for prevention, diagnosis and cure of substance abuse. PUBLIC HEALTH RELEVANCE: Neuropeptides are signaling peptides that both influence and are influenced by drug abuse and complex behaviors. The proposed project strengthens the significant contributions of NIDA to the advancement of neuropeptide and drug abuse research by developing public bioinformatic resources and by integrating and further mining information from experiments already available. Outcomes from the proposed work will advance the identification and characterization of neuropeptide that support the prognostic, diagnostic and treatment of disorders associated with substance abuse.